POS0493 1H-NMR BASED METABOLOMIC PROFILE OF PATIENTS WITH GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA IN ACTIVE AND INACTIVE DISEASE STATE
Authors: O. Argyropoulou, M. Karagiannakou, D. Palamidas, D. Benaki, K. Tsezou, P. Vlachoyiannopoulos, E. Mikros, A. Tzioufas
Journal: Annals of the Rheumatic Diseases (2022)

Background Giant cell arteritis (GCA) is the most common form of systemic vasculitis in the elderly. The disease is characterized by a remarkable heterogeneity in terms of clinical picture, histologic pattern of the affected vessels, pathogenetic mechanisms and treatment selection strategies. Approximately half of GCA patients present with polymyalgia rheumatica (PMR), while 20% of PMR patients will develop GCA during follow-up. Organ or life-threatening complications of GCA, include vision loss, strokes, aneurysm formation and accelerated atherosclerosis. The clinical heterogeneity along with the increased relapse rate, even under treatment and the fact that ESR and C-Reactive Protein are the only laboratory tools for the assessment of active disease suggest that the definition of new biomarkers with diagnostic, prognostic and predictive value is an unmet need (1). Among the high throughput approaches towards this direction, 1 H NMR spectra of serum samples provides a direct, untargeted, and holistic metabolic profile offering a wealth of information that could be proved useful to discover outcome tools for the management of the disease (2). Objectives 1. To characterize and compare the metabolic profile of GCA/PMR serum samples, as captured in 1 H NMR spectra, in 3-time points: diagnosis, 1 and 6 months of treatment with steroids (remission), 2. evaluate whether 1 H NMR-based metabolomics in serum from patients with GCA/PMR associate with response to treatment and 3. identify potential discriminatory serum metabolic profiles correlating with disease activity. Methods One-hundred and ten serum samples from 50 consecutive patients (33-GCA and 17-PMR) were evaluated in the study. GCA serum samples consisted of 33 naïve, 22 in 1 and 21 after 6 months of treatment (25 females, mean age 73.0 ± 7.6 years and 8 males, mean age 69.5 ± 4.9 years), while PMR of 15 naive, 10 in 1st and 8 respectively (9 females, mean age 65.0 ± 5.3 years and 8 males, mean age 77.0 ± 6.6 years). The serum metabolic profiles of patients were obtained at a 600 MHz NMR spectrometer and analysed by means of uni- and multivariate statistical methods. Results Multivariate analysis showed metabolic differences between GCA/PMR patients in activity and in remission using unsupervised principal component analysis (PCA: R2X= 0.698, Q2= 0.561) and supervised partial least squares discriminant analysis (PLS-DA: R2X= 0.596, Q2= 0.219) (Figure 1). In accordance with univariate analysis (p&lt;0.05), the following discriminatory metabolites were identified: N-acetyl glycoproteins, 3-hydroxybutyric acid and phenylalanine were increased in inflammation, while cholines, lipoproteins, and lipids were decreased in these patients. Figure 1. (A) PLS-DA scores plot and (B) S-plot from OPLS-DA of 1 H NMR profiling of GCA/PMR serum samples before treatment (green dots) and after 1 (red dots) and 6 months (black dots) of treatment. Characteristic metabolites in inflammation and remission are annotated and the corresponding p-values are given. PLS-DA: partial least square discriminant analysis, OPLS-DA: orthogonal partial least squares discriminant analysis. Conclusion 1 H NMR-based serum metabolomics revealed a clear discrimination of GCA/PMR metabolic profiles before (active inflammation) and after treatment with steroids (remission), suggesting that the metabolomic analysis may serve as a useful tool to identify potential biomarkers related to disease activity in both GCA and PMR, as well as give further insights into pathogenetic mechanisms mediating the inflammatory response. Further validation studies to dissect the clinical value of specific metabolites are ongoing in our laboratory. References [1]Robinette ML et al. Front Immunol 2021 [2]Emwas A-M et al., Metabolites 2019 Disclosure of Interests None declared.